CJC-1295 NO-DAC / Ipamorelin Blend

<p><strong>CJC-1295 NO-DAC / Ipamorelin Blend</strong> combines two mechanistically distinct growth hormone secretagogues into a single co-administration protocol designed for acute pulsatile GH release research. CJC-1295 without DAC (also labeled Mod GRF 1-29 in many supplier catalogs) is a 29-amino-acid modified analog of growth hormone-releasing hormone (GHRH) that acts at the GHRH receptor (GHRHR) on pituitary somatotrophs. Ipamorelin is a pentapeptide selective agonist of the ghrelin receptor (GHS-R1a) that stimulates GH release via a distinct G-protein-coupled receptor pathway. Together, the two compounds target both major GH secretagogue receptor pathways simultaneously, producing synergistic pulsatile GH release that exceeds either compound alone.</p>

<h2>Mechanism of Action</h2>

<h3>CJC-1295 NO-DAC (Mod GRF 1-29) — GHRH Receptor Agonist</h3>

<p>CJC-1295 without DAC is a truncated and stabilized version of the native 44-amino-acid GHRH, retaining the first 29 residues (GRF 1-29) and incorporating 4 amino acid substitutions that improve proteolytic stability relative to the native sequence: Ala2 to D-Ala (DPP-IV resistance), Gln8 to Ala (stability), Ala15 to Gln (solubility), and Leu27 to Leu/Arg27 to Arg (receptor binding optimization). The "no-DAC" designation specifically distinguishes this compound from a different product — CJC-1295 with Drug Affinity Complex (DAC) — that includes a lysine-derivatized linker enabling reversible albumin binding and a multi-day half-life.</p>

<p>Without the DAC modification, this GHRH analog has a pharmacokinetic profile much closer to native GHRH — a half-life measured in minutes to low tens of minutes rather than days. In research designs, this short half-life means that a single injection produces an acute GHRH stimulus that resolves within 30–60 minutes, modeling physiological GHRH pulsatility rather than the sustained supraphysiological elevation produced by the DAC version. Teichman and colleagues (PMID 16822193) characterized the pharmacodynamics of the DAC-modified version and established the albumin-binding mechanism; the no-DAC version lacks this mechanism and is appropriate for research requiring pulse-patterned GHRH stimulation.</p>

<h3>Ipamorelin — Selective GHS-R1a Agonist</h3>

<p>Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) that agonizes the ghrelin receptor (GHS-R1a) in pituitary somatotrophs with high selectivity and minimal co-stimulation of ACTH, cortisol, or prolactin release — a key pharmacological property that distinguishes it from earlier ghrelin-mimetic peptides like GHRP-6 and GHRP-2, which show significant cortisol-releasing activity. Raun and colleagues (PMID 9849822) characterized ipamorelin as the first selective GHS-R1a agonist without the ACTH/cortisol co-release profile, making it useful for pituitary GH secretion studies without hypothalamic-pituitary-adrenal (HPA) axis confounding.</p>

<h3>Synergistic Dual-Receptor Mechanism</h3>

<p>GHRH and ghrelin receptor pathways converge on pituitary somatotrophs through different intracellular second-messenger cascades: GHRH acts through Gs-coupled adenylyl cyclase activation (cAMP/PKA pathway), while GHS-R1a acts through Gq-coupled phospholipase C activation (IP3/DAG/PKC pathway and intracellular calcium mobilization). When both pathways are activated simultaneously, the cellular calcium spike and cAMP rise are larger and more sustained than either stimulus alone, producing supra-additive (synergistic) GH secretion. This dual-receptor synergy is the primary rationale for the combination in research protocols studying pulsatile GH axis stimulation.</p>

<h2>Research Applications</h2>

<ul> <li><strong>Pulsatile GH secretion studies</strong> — modeling physiological GH pulse patterns; comparing acute vs. sustained GHRH paradigms (no-DAC vs. DAC forms in parallel groups); characterizing somatotroph response kinetics by serial GH sampling post-injection</li> <li><strong>GHRH receptor pharmacology</strong> — GHRHR agonist potency comparisons (Mod GRF 1-29 vs. native GHRH vs. sermorelin vs. tesamorelin); receptor desensitization and downregulation studies under repeat dosing</li> <li><strong>GHS-R1a pharmacology</strong> — selective ghrelin receptor agonist characterization; GHS-R1a signaling pathway studies (IP3, calcium flux, ERK phosphorylation) in pituitary cell lines; selectivity profiling for ACTH/cortisol co-stimulation</li> <li><strong>GH/IGF-1 axis research</strong> — GH pulse amplitude and frequency analysis; downstream IGF-1 and IGFBP-3 response characterization; somatostatin regulation of GHRH-stimulated GH release</li> <li><strong>Hypothalamic-pituitary function research</strong> — combined vs. single-receptor stimulation designs; pituitary reserve testing models; comparison with insulin tolerance test (ITT) as a GH secretagogue paradigm</li> <li><strong>Body composition and metabolic research</strong> — GH-stimulated lipolysis in adipose tissue; hepatic IGF-1 induction; protein anabolism under GH pulsatility manipulation in rodent models</li> <li><strong>Aging and GH axis decline</strong> — somatopause models; response to combined GHRH+GHS-R1a stimulation in aged animals showing blunted somatotroph responsiveness</li> </ul>

<h2>Critical Research Design Consideration: No-DAC vs. DAC Forms</h2>

<p>The most important design decision when using GHRH analogs is whether the experimental question requires acute pulsatile stimulation (no-DAC form, t½ minutes) or sustained supraphysiological GHRH exposure (DAC form, t½ days). These are pharmacologically different experiments:</p>

<ul> <li><strong>No-DAC (this blend)</strong>: appropriate when modeling physiological GH pulsatility, testing somatotroph acute responsiveness, studying GHRH receptor kinetics without chronic desensitization, or combining with ipamorelin for synergistic acute release</li> <li><strong>DAC form</strong>: appropriate when studying sustained GH axis activation, dose-response at steady-state GH elevation, or pharmacokinetic/pharmacodynamic modeling of long-acting GHRH analogs</li> </ul>

<p>Confusing the two forms is a common experimental error in the research literature. Verify the product description explicitly states "no DAC" or "Mod GRF 1-29" and not "CJC-1295 with DAC" before ordering for acute stimulation protocols.</p>

<h2>Market Context</h2>

<p>The CJC-1295 NO-DAC / Ipamorelin blend is a moderately traded research combination. Peptides.SO tracks <strong>8 active supplier listings</strong> with pricing from $10 to approximately $86 per listing (avg ~$45). The lower listing count compared to BPC-157 or standard ipamorelin reflects the niche positioning of pre-blended GHRH+GHS-R1a combinations versus researchers who prefer to buy each compound independently for flexible dosing. Vial sizes commonly available: 2mg CJC-1295 NO-DAC / 2mg ipamorelin to 5mg / 5mg blended formats. Researchers requiring dose titration of each component independently should procure them separately.</p>

<h2>Frequently Asked Questions</h2>

<p><strong>What is the difference between CJC-1295 with DAC and CJC-1295 without DAC (Mod GRF 1-29)?</strong><br/> The DAC (Drug Affinity Complex) modification adds a reactive ester group to a specific lysine residue that forms a covalent bond with serum albumin, extending the half-life from minutes to approximately 5-8 days. Without DAC, the peptide is cleared rapidly (half-life 30-90 minutes), producing an acute GHRH stimulus. These are different pharmacological tools for different experimental questions. This blend contains the no-DAC form exclusively, appropriate for pulsatile GH stimulation protocols.</p>

<p><strong>Why is ipamorelin preferred over GHRP-6 or GHRP-2 in combination studies?</strong><br/> Ipamorelin selectively activates GHS-R1a without significantly stimulating ACTH or cortisol release, properties that GHRP-6 and GHRP-2 lack. When studying GH axis activation in isolation, ipamorelin produces cleaner experimental data because cortisol co-stimulation does not confound downstream anabolic or metabolic measurements. For research specifically investigating HPA axis co-activation alongside GH secretion, GHRP-2 or GHRP-6 would be appropriate alternatives.</p>

<p><strong>What GH sampling protocol is used with this combination in rodent studies?</strong><br/> Published rodent GH-stimulation studies using GHRH + ghrelin-mimetic combinations typically collect blood samples at 0, 15, 30, 45, 60, 90, and 120 minutes post-injection for GH radioimmunoassay or ELISA. Peak GH is usually observed at 15-30 minutes post-injection. The GH pulse resolves within 60-120 minutes, consistent with the short half-life of the no-DAC GHRH analog.</p>

<p><strong>Are these compounds stable when co-formulated in the same vial?</strong><br/> Lyophilized co-formulation of CJC-1295 NO-DAC and ipamorelin in the same vial is chemically stable when stored correctly (−20°C, dark, dry). After reconstitution, the combined solution should be stored at 4°C and used within 2-4 weeks. The two peptides do not chemically react with each other under storage conditions and can be co-reconstituted in sterile bacteriostatic water.</p>

<h2>Related Research on Peptides.SO</h2>

<p>See also: <a href="/peptide/cjc-1295-dac">CJC-1295 with DAC (long-acting form)</a> · <a href="/peptide/cjc-1295-no-dac">CJC-1295 NO-DAC (single compound)</a> · <a href="/peptide/sermorelin">Sermorelin (GHRH analog)</a> · <a href="/peptide/tesamorelin">Tesamorelin</a> · <a href="/learn/cjc-1295-dac-ghrh-analog-research">CJC-1295 DAC Research Guide</a></p>

<h2>Cited Research</h2>

<ul> <li>Teichman SL, et al. "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone." <em>J Clin Endocrinol Metab.</em> 2006. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/16822193/" rel="noopener">16822193</a></li> <li>Raun K, et al. "Ipamorelin, the first selective growth hormone secretagogue." <em>Eur J Endocrinol.</em> 1998. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/9849822/" rel="noopener">9849822</a></li> <li>Bowers CY, et al. "Growth hormone-releasing peptides and their analogs." <em>Front Neuroendocrinol.</em> 1991. PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/2050566/" rel="noopener">2050566</a></li> <li>Veldhuis JD, et al. "Somatostatin and GHRH: twin regulators of pulsatile GH secretion." <em>Best Pract Res Clin Endocrinol Metab.</em> 1999.</li> </ul>

<p><em>For research purposes only. CJC-1295 NO-DAC and ipamorelin are not approved for human or veterinary therapeutic use, are not drugs or dietary supplements, and have not been evaluated by any regulatory authority for safety or efficacy in humans or animals outside controlled laboratory settings.</em></p>